Investigations carried out in this laboratory have been directed toward evaluating the use of combined modality treatments, i.e., immunochemotherapy, on the growth of a primary tumor and metastases. It was observed that when C. parvum (CP) was administered i.p. asynchronously in combination with cyclophosphamide (CY) at weekly intervals to C3HeB mice bearing an established growing C3H mammary adenocarcinoma, tumor growth inhibition was achieved which was greater than that resulting from either agent alone. In additional investigations, other chemotherapeutic and non-specific stimulating agents were substituted for or added to the CY, CP combination. None, when substituted, produced results equal to that combination, nor did their addition improve the results. We have attempted to identify host responses resulting from the therapy which might be responsible for the overall effectiveness of the combination. None of the investigations provided clear evidence implicating any of the host factors for the general success of treatment. Of particular interest has been the observation that in all experiments employing this combination of therapy, the effect on tumor growth varied from mouse to mouse despite the fact that tumors in any one study were from the same inoculum and were in syngeneic hosts. Whether this divergence was the result of disparate host modulation or differences in tumor characteristics was speculative. The present investigations with two C3H mammary tumors in the same host indicate that the tumors rather than the host are responsible for the observed variation in treatment effectiveness. They suggest that each inoculum contains a heterogeneous tumor cell population so that aliquots of the suspension upon transfer produce by chance clones giving rise to tumors having variable susceptability to the therapy. Preliminary investigations evaluating tumor cell kinetics has shown that the cytokinetics of those tumors responding best to treatment differ from those responding least. Investigations during the coming year will continue to assess tumor and host factors in responders and non-responders to chemo-immunotherapy.